What is the most likely diagnosis for a 47-year-old male with a history of high sun exposure, new onset headaches that are worse in the mornings, personality changes, ataxic gait, and visual field deficits, who also has a new lesion behind his right ear and posterior auricular lymphadenopathy, with a past medical history of asthma, type 2 diabetes, and hypertension?

Illness Script: Brain Metastasis from Melanoma (Most Likely Diagnosis)

Mechanism(s) of Disease

Melanoma cells disseminate hematogenously from a primary cutaneous site (or regional lymph nodes) to the brain parenchyma, most commonly lodging at the gray-white matter junction in vascular watershed zones. 1 The metastatic deposits cause local mass effect, peritumoral edema, and increased intracranial pressure, leading to progressive neurological dysfunction. 1 Melanoma has a particular propensity for brain metastasis, with 10-40% of stage IV melanoma patients developing clinically evident brain metastases and up to 90% showing brain involvement at autopsy. 2 The posterior auricular lymphadenopathy in this patient suggests regional spread from a primary melanoma lesion behind the ear, establishing stage III disease that has now progressed to stage IV with brain involvement. 3

Key Features Commonly Found in History (Including Risk Factors)

• Progressive morning headaches worsening over weeks (4 weeks in this case), worse with Valsalva maneuvers like bending over 1, 2
• Personality changes and behavioral abnormalities (irritability, anger outbursts, memory impairment such as forgetting anniversary) 1, 2
• Ataxia and gait instability (unsteadiness, near-falls, bumping into things) 1, 2
• High sun exposure history (works as white-water rafter, only occasional sunscreen use) 1, 3
• New skin lesion behind ear with posterior auricular lymphadenopathy - highly suggestive of melanoma with regional nodal metastasis 3
• Weight loss (5kg over 6 months) 1
• Nausea without vomiting (common with increased intracranial pressure) 1
• Headache severity fluctuating with time of day (8/10 morning, 4/10 evening - classic for increased ICP) 2

Physical Exam Findings That Make This Condition More Likely

• Bilateral temporal visual field deficits - indicates chiasmal or retrochiasmal involvement from leptomeningeal spread or mass effect 2
• Posterior auricular lymphadenopathy on right side - regional nodal involvement from primary melanoma 3
• Small lesion behind right ear - likely primary melanoma site 3
• Cerebellar signs: left-sided ataxia on finger-to-nose, tremor on heel-to-shin test, ataxic gait 1, 2
• Flat affect and personality changes - frontal lobe or diffuse cerebral involvement 2
• Decreased breath sounds in right middle lobe with diffuse crackles - raises concern for pulmonary metastases 1
• Normal motor strength bilaterally - helps distinguish from stroke 1

Helpful Diagnostic Studies to Confirm Diagnosis

First-Line Imaging (Urgent)

• MRI brain with gadolinium contrast at ≥1.5-T field strength - gold standard for detecting brain metastases 1, 2
  • Required sequences: pre- and post-contrast T1-weighted, T2-weighted/T2-FLAIR, diffusion-weighted imaging (DWI) 1, 2
  • Post-gadolinium 3D T1-weighted sequences for detecting small lesions 2
  • Characteristic findings: solid or ring enhancement, perifocal edema, predilection for gray-white matter junction 1

Systemic Staging

• Chest CT - evaluate pulmonary findings (decreased breath sounds, crackles) and exclude metastatic disease 2
• Complete spine MRI with gadolinium - assess for spinal leptomeningeal disease given multifocal neurological deficits 2
• PET-CT - systemic staging for confirmed melanoma 2

Tissue Diagnosis

• Excisional biopsy of ear lesion with 2mm margin - establish primary melanoma diagnosis, obtain Breslow thickness 1, 3
• Fine-needle aspiration of posterior auricular lymph node - confirm nodal metastasis 3
• CSF cytology with immunocytochemical staining for melanocytic markers - if leptomeningeal enhancement seen on MRI or imaging equivocal 2

Additional Studies

• Formal neurological examination using standardized form (e.g., RANO group evaluation) 1
• Histopathology of excised lesion - confirm melanocytic nature, malignancy, Breslow thickness, Clark level, ulceration presence 3

Pre-Test Probability: HIGH

Evidence Supporting This Diagnosis:

• Clinical presentation is classic: progressive morning headaches over 4 weeks, personality changes, ataxia, and visual field deficits are pathognomonic for brain metastases with increased intracranial pressure 1, 2
• Dermatologic findings are highly specific: new lesion behind ear + ipsilateral posterior auricular lymphadenopathy strongly suggests melanoma with regional spread 3
• High-risk occupational sun exposure without adequate protection is a major melanoma risk factor 1, 3
• Multifocal neurological deficits (cerebellar, visual, cognitive) suggest multiple brain lesions or leptomeningeal involvement, characteristic of metastatic disease 2
• Rapid symptom progression over weeks is more typical of metastatic disease than primary brain tumors 2
• Weight loss supports systemic malignancy 1
• Pulmonary findings (decreased breath sounds, crackles) raise concern for concurrent lung metastases 1

Evidence Against This Diagnosis:

• No documented prior melanoma diagnosis - however, approximately 10% of melanomas present with nodal or distant metastases at initial diagnosis 3
• Relatively young age (47) - though melanoma can occur at any age, average age for brain metastases is 45.1 years 4
• No history of head trauma - but this actually makes chronic subdural hematoma less likely and supports the metastatic diagnosis 1

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Illness Script: Glioblastoma (Second Most Likely Diagnosis)

Mechanism(s) of Disease

Malignant transformation of glial cells leads to a rapidly proliferating, infiltrative tumor with necrosis, vascular proliferation, and mass effect. 2 Glioblastomas typically arise de novo in the cerebral hemispheres and cause progressive neurological dysfunction through local tissue destruction, peritumoral edema, and increased intracranial pressure. 2 The tumor's infiltrative nature makes complete surgical resection impossible, and its aggressive biology leads to rapid clinical deterioration. 2

Key Features Commonly Found in History (Including Risk Factors)

• Progressive neurological symptoms over weeks to months 2
• Personality and mood changes reflecting frontal lobe or diffuse cerebral involvement 2
• Headaches worse in morning due to increased intracranial pressure 2
• Middle-aged adults (average age 45-50 years) 2
• No prior cancer history - glioblastoma is a primary brain tumor 2
• Cognitive decline and memory impairment 2
• Seizures (though not present in this case) 1

Physical Exam Findings That Make This Condition More Likely

• Focal neurological deficits corresponding to tumor location 2
• Personality changes and flat affect - frontal lobe involvement 2
• Ataxia - cerebellar or brainstem involvement 2
• Visual field deficits - optic pathway involvement 2
• Progressive worsening of symptoms over weeks 2

Helpful Diagnostic Studies to Confirm Diagnosis

First-Line Imaging

• MRI brain with and without IV contrast - gold standard for detecting and characterizing primary brain tumors 2
  • Required sequences: axial T1-weighted, axial FLAIR, post-gadolinium 3D T1-weighted 2
  • Characteristic findings: irregular ring enhancement, central necrosis, perilesional edema, mass effect 2
• MR perfusion imaging - elevated relative cerebral blood volume (rCBV) indicates high-grade tumor 2
• Magnetic resonance spectroscopy (MRS) - can help characterize tumor and distinguish from other lesions 2

Tissue Diagnosis

• Stereotactic biopsy or surgical resection - required for definitive diagnosis and molecular profiling 2
• Histopathological examination - confirms glial origin, grade, molecular markers (IDH mutation, MGMT methylation) 2

Pre-Test Probability: MEDIUM

Evidence Supporting This Diagnosis:

• Progressive neurological symptoms over 4 weeks with personality changes and focal deficits fit glioblastoma presentation 2
• Age 47 is within typical range for glioblastoma 2
• Multifocal neurological deficits could represent a large infiltrative tumor 2
• Morning headaches with increased severity suggest increased intracranial pressure from mass effect 2

Evidence Against This Diagnosis:

• Presence of skin lesion with lymphadenopathy strongly suggests systemic malignancy rather than primary brain tumor 3
• Weight loss and pulmonary findings more consistent with metastatic disease 1
• Bilateral temporal visual field loss suggests chiasmal involvement, which would be unusual for a single glioblastoma 2
• High sun exposure history is irrelevant to glioblastoma but highly relevant to melanoma 1
• Rapid progression over 4 weeks is somewhat fast even for glioblastoma, which typically evolves over weeks to months 2

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Illness Script: Chronic Subdural Hematoma (Least Likely Diagnosis)

Mechanism(s) of Disease

Slow accumulation of blood in the subdural space following minor or unrecognized head trauma causes gradual mass effect and increased intracranial pressure. 2 The hematoma develops from tearing of bridging veins, often in elderly patients or those with brain atrophy. 2 The collection gradually expands through repeated microhemorrhages from the vascular membrane surrounding the hematoma, leading to progressive neurological symptoms over weeks to months. 2

Key Features Commonly Found in History (Including Risk Factors)

• History of minor head trauma (though 30-40% have no clear trauma history) 2
• Gradually worsening headaches over weeks to months 2
• Personality changes and cognitive decline 2
• Gait instability and falls 2
• Fluctuating level of consciousness 2
• Advanced age (more common in elderly) 2
• Anticoagulation use (not present in this case) 2
• Alcohol use (patient drinks 1-2 glasses wine nightly - mild consumption) 2

Physical Exam Findings That Make This Condition More Likely

• Gait ataxia and imbalance 2
• Fluctuating mental status 2
• Hemiparesis (not present in this case) 2
• Papilledema from increased intracranial pressure 2

Helpful Diagnostic Studies to Confirm Diagnosis

First-Line Imaging

• Non-contrast CT head - initial imaging modality of choice for suspected subdural hematoma 2
  • Characteristic findings: crescent-shaped hypodense (chronic) or isodense (subacute) collection along cerebral convexity 2
• MRI brain - provides superior characterization of subdural collections 2
  • Required sequences: axial T1-weighted, axial FLAIR, post-gadolinium 3D T1-weighted 2
  • Can distinguish acute, subacute, and chronic blood products 2

Additional Studies

• Coagulation studies - assess bleeding risk if surgical evacuation planned 2

Pre-Test Probability: LOW

Evidence Supporting This Diagnosis:

• Gradually worsening headaches over 4 weeks could fit chronic subdural hematoma 2
• Personality changes and gait instability are common presentations 2
• No clear trauma history - 30-40% of chronic subdural hematomas occur without recognized trauma 2
• Mild alcohol use could be a minor risk factor 2

Evidence Against This Diagnosis:

• Bilateral temporal visual field loss is NOT explained by subdural hematoma, which causes focal mass effect but not specific chiasmal involvement 2
• Skin lesion with posterior auricular lymphadenopathy has no relationship to subdural hematoma 3
• Weight loss and pulmonary findings are inconsistent with isolated subdural hematoma 1
• Multifocal neurological deficits (cerebellar, visual, cognitive) suggest multiple lesions or leptomeningeal disease rather than a single subdural collection 2
• Age 47 is younger than typical for chronic subdural hematoma 2
• No anticoagulation use and no significant trauma history make this diagnosis less likely 2
• Morning predominance of headaches with Valsalva worsening is more characteristic of increased ICP from tumor than subdural hematoma 2